Division of Genetic Medicine (G.L.C., J. Saykally, M.Z., H.C.M.), Department of Pediatrics, University of Washington, Seattle; Epilepsy Research Centre (D.E.C., B.M.R., J.M.M., A.L.S., S.A.M., S.F.B., I.E.S.), Department of Medicine, The University of Melbourne, Austin Health, Melbourne, Australia; Neurology Department (D.E.C.), Northern Health, Melbourne, Australia; Epilepsy Research Program (L.D.), School of Pharmacy and Medical Sciences, and Sansom Institute for Health Research (L.D.), University of South Australia, Adelaide, Australia; Department of Neurology (K.B.H., R.J.L., A.S.H., I.E.S.), Royal Children's Hospital, Melbourne, Australia; Florey Institute of Neuroscience and Mental Health (K.B.H., S.M., R.J.L., A.S.H., S.A.M., I.E.S.), Melbourne, Australia; Murdoch Childrens Research Institute (K.B.H., R.J.L., A.S.H.), Melbourne, Australia; Department of Paediatrics (S.M., R.J.L., A.S.H.) and Department of Radiology (S.M.), The University of Melbourne, Melbourne, Australia; and Epilepsy Division (J. Sullivan), Department of Neurology and Pediatrics, University of California, San Francisco.
Neurol Genet. 2015 Jul 23;1(2):e17. doi: 10.1212/NXG.0000000000000016. eCollection 2015 Aug.
To assess the presence of DEPDC5 mutations in a cohort of patients with epileptic spasms.
We performed DEPDC5 resequencing in 130 patients with spasms, segregation analysis of variants of interest, and detailed clinical assessment of patients with possibly and likely pathogenic variants.
We identified 3 patients with variants in DEPDC5 in the cohort of 130 patients with spasms. We also describe 3 additional patients with DEPDC5 alterations and epileptic spasms: 2 from a previously described family and a third ascertained by clinical testing. Overall, we describe 6 patients from 5 families with spasms and DEPDC5 variants; 2 arose de novo and 3 were familial. Two individuals had focal cortical dysplasia. Clinical outcome was highly variable.
While recent molecular findings in epileptic spasms emphasize the contribution of de novo mutations, we highlight the relevance of inherited mutations in the setting of a family history of focal epilepsies. We also illustrate the utility of clinical diagnostic testing and detailed phenotypic evaluation in characterizing the constellation of phenotypes associated with DEPDC5 alterations. We expand this phenotypic spectrum to include epileptic spasms, aligning DEPDC5 epilepsies more with the recognized features of other mTORopathies.
评估癫痫性痉挛患者队列中 DEPDC5 突变的存在。
我们对 130 名痉挛患者进行了 DEPDC5 重测序、感兴趣变异的分离分析以及可能和可能致病变异患者的详细临床评估。
我们在 130 名痉挛患者的队列中发现了 3 名患者存在 DEPDC5 变异。我们还描述了另外 3 名患有 DEPDC5 改变和癫痫性痉挛的患者：2 名来自先前描述的家族，1 名通过临床检测发现。总体而言，我们描述了 5 个家族的 6 名痉挛和 DEPDC5 变异患者；2 例为新生突变，3 例为家族性。2 名患者存在局灶性皮质发育不良。临床结局高度可变。
虽然最近癫痫性痉挛的分子发现强调了新生突变的贡献，但我们强调了家族性局灶性癫痫史背景下遗传突变的相关性。我们还说明了临床诊断测试和详细表型评估在描述与 DEPDC5 改变相关的表型组合中的作用。我们将该表型谱扩展到包括癫痫性痉挛，使 DEPDC5 癫痫与其他 mTOR 相关疾病的公认特征更一致。
